[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to perform a meta-analysis of current literature to determine whether lowering blood pressure (BP) during the acute phase of an ischemic stroke improves short- and long-term outcomes.PubMed, Cochrane, and Embase were searched until September 5, 2014 using combinations of the search terms: blood pressure reduction, reduced blood pressure, lowering blood pressure, ischemic stroke, acute stroke, and intra-cerebral hemorrhage. Inclusion criteria were randomized controlled trial and patients with acute stroke (ischemic or hemorrhagic) treated with an antihypertensive agent or placebo. Outcome measures were change in systolic and diastolic BP (SBP, DBP) after treatment, and short- and long-term dependency and mortality rates.A total of 459 studies were identified, and ultimately 22 studies were included in the meta-analysis. The total number of participants in the treatment groups was 5672 (range, 6-2308), and in the control groups was 5416 (range, 6-2033). In most studies, more than 50% of the participants were males and the mean age was more than 60 years. The mean follow-up time ranged from 5 days to 12 months. As expected, treatment groups had a greater decrease in BP than control groups, and this effect was seen with different classes of antihypertensive drugs. Short-term and long-term dependency rates were similar between treatment and control groups (short-term dependency: pooled odds ratio [OR] = 1.041, 95% confidence interval [CI]: 0.936-1.159, P = 0.457; long-term dependency: pooled OR = 1.013, 95% CI: 0.915-1.120, P = 0.806). Short-term or long-term mortality was similar between the treatment and control groups (short-term mortality: pooled OR = 1.020, 95% CI: 0.749-1.388, P = .902; long-term mortality: pooled OR = 1.039, 95% CI: 0.883-1.222, P = 0.644).Antihypertensive agents effectively reduce BP during the acute phase of an ischemic stroke, but provide no benefit with respect to short- and long-term dependency and mortality.
Medicine 06/2015; 94(23):e896. DOI:10.1097/MD.0000000000000896 · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Although a variety of drugs have been used to treat the symptoms of rheumatoid arthritis (RA), none of them are able to cure the disease. Interferon ß (IFN-ß) has pleiotropic effects on RA, but whether it can be used to treat RA remains globally controversial. Thus, in this study we tested the effects of IFN-ß on RA patients and on collagen antibody-induced arthritis (CAIA) model mice.Methods
The cytokine and auto-antibody expression profiles in the serum and synovial fluid (SF) from RA patients were assessed using enzyme-linked immunosorbent assay (ELISA) and compared with the results from osteoarthritis (OA) patients. Exogenous IFN-ß was administered to RA patients and CAIA model mice, and the therapeutic effects were evaluated. Endogenous IFN-ß expression in the joint bones of CAIA model mice was evaluated by quantitative real-time PCR (qRT-PCR). The effects of exogenous IFN-ß on CAIA model mice were assessed using a clinical scoring system, hematoxylin eosin and safranin-O with fast green counterstain histology, molybdenum target X-ray, and tartrate-resistant acid phosphatase (TRAP) staining. The RANKL-RANK signaling pathway was analyzed using qRT-PCR. The RAW 264.7 cell line was differentiated into osteoclasts with RANKL stimulation and then treated with exogenous IFN-ß.ResultsThe expression of inflammatory cytokines (IFN-¿, IL-17, MMP-3, and RANKL) and auto-antibodies (CII antibodies, RF-IgM, and anti-CCP/GPI) were significantly higher in RA compared with OA patients. After IFN-ß intervention, some clinical symptoms in RA patients were partially alleviated, and the expression of IFN-¿, IL-17, MMP-3, and OPG) returned to normal levels. In the CAIA model, the expression of endogenous IFN-ß in the joint bones was decreased. After IFN-ß administration, the arthritis scores were decreased; synovial inflammation, cartilage, and bone destruction were clearly attenuated; and the expression of c-Fos and NFATc1 were reduced, while RANKL and TRAF6 expression was unchanged. In addition, exogenous IFN-ß directly inhibited RANKL-induced osteoclastogenesis.Conclusions
Exogenous IFN-ß administration immunomodulates CAIA, may reduce joint inflammation and, perhaps more importantly, bone destruction by inhibiting the RANKL-c-Fos signaling pathway. Exogenous IFN-ß intervention should be selectively used on RA patients because it may only be useful for RA patients with low endogenous IFN-ß expression.
Journal of Translational Medicine 12/2014; 12(1):330. DOI:10.1186/s12967-014-0330-y · 3.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies have indicated that dynamic alterations in the structure of postsynaptic density (PSD) are involved in the pathogenesis of many central nervous system disorders, including ischemic stroke. Homer is the newly identified scaffolding protein located at PSD and regulates synaptic function. Homer1a, an immediate early gene, has been shown to be induced by several stimulations, such as glutamate, brain-derived neurotrophic factor, and trauma. However, whether acidosis mediated by acid-sensing ion channels (ASICs) and hypoxia during cerebral ischemia can change Homer1a expression remains to be determined.
We investigated that acidosis and hypoxia selectively and rapidly upregulated Homer1a expression, but not Homer1b/c in cultured cortical neurons. We also found that Homer1a exhibited induction expression in brain cortex of the middle cerebral artery occlusion (MCAO) rats. Additionally, acid-evoked Homer1a mRNA induction depended on extracellular signal-regulated kinase1/2 (ERK1/2) and Akt activity, and ASIC1a-mediated calcium influx whereas hypoxia depended only on ERK1/2 activity. Also, we demonstrated that continuous acidosis and hypoxia resulted in pronounced cell injury and Homer1a knockdown with small interfering RNA aggravated this damage induced by 3 h acid and hypoxia incubation in neuro-2a cells.
Homer1a might act as an activity-dependent regulator responding to extracellular stimuli during cerebral ischemia.
[Show abstract][Hide abstract] ABSTRACT: Background
There are two widely used transient middle cerebral artery occlusion (MCAO) methods, which differ in the use of unilateral or bilateral carotid artery reperfusion (UNICAR and BICAR). Of the two methods, UNICAR is easier to perform. This study was designed to comprehensively compare the two reperfusion methods to determine if there are any differences in outcomes.
The UNICAR and BICAR groups each included 9 rats. At baseline, the average pO2 was 20.54 ± 9.35 and 26.43 ± 7.39, for the UNICAR and BICAR groups, respectively (P = 0.519). Changes in pO2, as well as other physiological parameters measured within the ischemic lesion, were similar between the UNICAR and BICAR groups during 90 min of MCAO and the first 30 min of reperfusion (all P > 0.05). Furthermore, both the Bederson score and Garcia score, which are used for neurological assessment, were also similar (both P > 0.05). There were also no significant differences in T2WI lesion volume, DWI lesion volume, PWI lesion volume, or TTC staining infarct volume between the two groups (all P > 0.05).
UNICAR and BICAR have similar capability for inducing acute brain ischemic injury and can be considered interchangeable up to 24 hours after reperfusion.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Whether small vessel infarction (SVI) correlates with large arterial lesion is under debate. The aim of the present study was to analyze the relationship between the single SVI in carotid territory by diffusion weight imaging (DWI) and arterial lesion by contrast enhanced magnetic resonance angiography (CEMRA).
Sixty patients with acute cerebral infarction underwent DWI within 7 days and CEMRA within 2 weeks after onset. They were divided into 2 groups of patients with and without single SVI. The clinical and magnetic resonance image features were compared between two groups.
Lesions of ipsilateral extracranial carotid artery were detected in 10 patients of SVI groups (36%) versus 8 patients (25%) of non-SVI group (P = 0.54). Incidence of intracranial vascular lesion in single SVI group (32%) was slightly lower than that of non-SVI group (47%) (P = 0.52). And 46 patients (77%) were assessed on plaque of carotid artery. Incidence of ipsilateral carotid artery plaque (44%) was higher in single SVI group than that of non-SVI group (35%) (P = 0.76). And the incidence of vulnerable plaque in single SVI group (26%) was similar to that of non-SVI group (22%) (P = 0.73).
SVI has not a single underlying mechanism of stroke. However, further studies with a large number of patients are warranted.
Zhonghua yi xue za zhi 12/2012; 92(47):3358-3360. DOI:10.3760/cma.j.issn.0376-2491.2012.47.014
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Vertebral artery hypoplasia (VAH), which has been found in about 10 % of normal individuals, does not produce symptoms but may be associated with an increased risk of cerebral posterior circulation ischemic (PCI) stroke. The aims of this study were to determine the prevalence of VAH in Chinese patients with cerebral infarction and investigate whether VAH is an independent risk factor for PCI stroke.
The medical records of 841 Chinese stroke patients were reviewed retrospectively. All patients underwent either cervical contrast-enhanced magnetic resonance angiography (CE-MRA) or cervical computed tomography angiography (CTA). There is no standard definition of VAH; we defined it as a vertebral artery < 2 mm in diameter and the whole artery was slim or absent on CE-MRA or CTA. Univariate and multivariate logistic regression analyses were performed to identify significant independent risk factors for PCI stroke.
There were 230 patients (27.3 %) diagnosed with PCI stroke and 91 patients diagnosed with VAH (10.8 %). Multivariate logistic regression analysis showed that VAH, male gender, and stenosis of the posterior circulation were independent risk factors for PCI stroke.
Our results show that VAH is not rare in Chinese patients with stroke and that its presence increases the risk of PCI stroke.
[Show abstract][Hide abstract] ABSTRACT: Background/aim:
It remains unclear how wallerian degeneration of the pyramidal tract (PT) in the acute phase of supratentorial intracranial hemorrhage (ICH) correlates with the long-term functional outcome. The aim of this study was to quantify and predict the long-term neuromotor outcome using diffusion tensor imaging (DTI) during the early stages of ICH.
Twenty-seven patients with a hemiparetic ICH were prospectively studied using DTI either within 3 days or at 2 weeks after onset. A region-of-interest-based analysis was performed for fractional anisotropy (FA) of the PT in the cerebral peduncle. The degree of paresis was assessed upon admission and at 6 months using paresis grading (PG), and the functional outcome was evaluated using the modified Rankin Scale (mRS). The activities of daily living were evaluated using the Functional Independence Measure (FIM).
The FA values within 3 days and after 2 weeks of ICH onset were significantly decreased at the affected side (p = 0.001, reduced by 11%; p < 0.001, reduced by 14%, respectively), but the mean diffusivity at the same time points remained unchanged (p = 0.05 and p = 0.136, respectively). The ratio of the FA (rFA) at the affected side to that of the unaffected side within 3 days was negatively correlated with the PG (p < 0.001, r = -0.642), positively correlated with the FIM scores (p = 0.004, r = 0.532), and negatively correlated with the mRS scores at the end of follow-up (median = 17 months) (p = 0.010, r = -0.490). The rFA at 2 weeks was positively correlated with the FIM (p < 0.001, r = 0.661) and negatively correlated with mRS scores and PG at the end of follow-up (p < 0.001, r = -0.653; p < 0.001, r = -0.700). For both patients with good and poor outcomes based on the PG, the area under the receiver operating characteristic (ROC) curve for rFA at 2 weeks was greater than the area under the ROC for rFA within 3 days, and the cutoff point for the rFA at 2 weeks was set at 0.875 (sensitivity 76%, specificity 89%).
This study demonstrated that the use of DTI during the early stages of ICH may predict motor outcomes at 6 months after ICH. Moreover, as compared to use of DTI within 3 days of ICH onset, the application of DTI at 2 weeks after ICH could more accurately predict the motor outcomes and daily living activities of patients.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
In this study, we investigated whether pre-procedural imaging of LSAs would potentially be helpful for preventing LSAs from being covered.
We retrospectively evaluated the LSAs of 15 consecutive patients who underwent revascularization for symptomatic middle cerebral artery (MCA) stenosis. All patients underwent two- (2D) and three-dimensional (3D) digital subtraction angiography.
We found that 46.7 (7/15), 40 (6/15), and 13.3 % (2/15) of patients had stenotic lesions in the proximal, middle, and distal third of the M1 segment, respectively. There was a total of 32 LSAs that originated from the lesioned MCAs. Seven (21.9 %), 10 (31.3 %), 11 (34.4 %), and 4 (12.5 %) LSAs originated from the proximal third of the M1 segment, middle third of the M1 segment, distal third of the M1 segment, and starting segment of the superior M2 segment, respectively. Sixteen (76.2 %) of 22 LSAs in 13 patients were covered by stents. It would have been possible to avoid covering 43.8 % (7/16) of these LSAs with stents if they had been evaluated before stenting, and the stents had been accurately deployed. Among 16 LSAs which were covered by stent, only one (6.25 %) was occluded after coverage.
Our data suggest that evaluation of LSAs during MCA stenting would be potentially helpful for preventing LSAs from being covered and subsequently occluded by stents.
[Show abstract][Hide abstract] ABSTRACT: To study the efficacy of low-dose-rate californium-252 ((252)Cf) neutron intracavitary afterloading radiotherapy (RT) combined with external pelvic RT for treatment of cervical cancer.
The records of 96 patients treated for cervical cancer from 2006 to 2010 were retrospectively reviewed. For patients with tumors ≤4 cm in diameter, external beam radiation was performed (1.8 Gy/day, five times/week) until the dose reached 20 Gy, and then (252)Cf neutron intracavitary afterloading RT (once/week) was begun, and the frequency of external beam radiation was changed to four times/week. For patients with tumors >4 cm, (252)Cf RT was performed one to two times before whole-pelvis external beam radiation. The tumor-eliminating dose was determined by using the depth limit of 5 mm below the mucosa as the reference point. In all patients, the total dose of the external beam radiation ranged from 46.8 to 50 Gy. For (252)Cf RT, the dose delivered to point A was 6 Gy/fraction, once per week, for a total of seven times, and the total dose was 42 Gy.
The mean ± SD patient age was 54.7 ± 13.7 years. Six patients had disease assessed at stage IB, 13 patients had stage IIA, 49 patients had stage IIB, 3 patients had stage IIIA, 24 patients had stage IIIB, and 1 patient had stage IVA. All patients obtained complete tumor regression (CR). The mean ± SD time to CR was 23.5 ± 3.4 days. Vaginal bleeding was fully controlled in 80 patients within 1 to 8 days. The mean ± SD follow-up period was 27.6 ± 12.7 months (range, 6-48 months). Five patients died due to recurrence or metastasis. The 3-year survival and disease-free recurrence rates were 89.6% and 87.5 %, respectively. Nine patients experienced mild radiation proctitis, and 4 patients developed radiocystitis.
Low-dose-rate (252)Cf neutron RT combined with external pelvic RT is effective for treating cervical cancer, with a low incidence of complications.
International journal of radiation oncology, biology, physics 12/2011; 83(3):966-71. DOI:10.1016/j.ijrobp.2011.08.031 · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To review the clinical and genetic features of a pedigree of Kennedy disease in China.
The clinical data of patients from a Kennedy disease family were collected. The numbers of trinucleotide CAG repeats in exon 1 of the androgen receptor gene were determined by DNA sequencing and repeat fragment analysis.
In the pedigree, 4 patients were identified as Kennedy disease. Clinical manifested with adult-onset, progressive proximal limb muscle weakness and atrophy, gynecomastia, oligospermia were also presented. The number of trinucleotide CAG repeats in exon 1 of the androgen receptor gene was 51 in the proband. The electrophysiological study showed sensory and motor involvement and their serum triglycerides values were elevated significantly.
Androgen receptors gene testing is the most reliable diagnosing method, the patients suspected as Kennedy disease should have a gene testing of androgen receptors.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 09/2011; 40(5):555-8.
[Show abstract][Hide abstract] ABSTRACT: Radiation-induced necrosis is commonly seen after radiotherapy for nasopharyngeal carcinoma (NPC), but a post-irradiation brain abscess is rarely encountered and easily overlooked, which may lead to a dismal outcome. We describe two Chinese men with cerebral herniation caused by temporal lobe abscess within a radio-necrotic lesion presenting only with headache and neurological defects. Cranial magnetic resonance imaging (MRI) or computed tomography (CT) showed cystic lesions in the temporal lobe with a severe mass effect. Both patients had brain herniation before emergency operations. Therefore, our findings suggest that a post-irradiation brain abscess may insidiously develop into disastrous herniation, and regular multi-modality neuroimaging follow-up should be carried out to help avoid this situation.
[Show abstract][Hide abstract] ABSTRACT: Hydrocephalus is a common medical condition characterized by abnormalities in the secretion,circulation or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. The pathogenetic mechanism for the hydrocephalus is attributed to: the overproduction of CSF by the choroid plexus; the defect in CSF absorption and obstruction of CSF flow in the cerebral ventricles. However, the underlying etiology is poorly understood. With the development of genetic engineering, a growing body of evidence indicates that genetic factors play an essential role in the pathogenesis of hydrocephalus. It is the aim of this review to summarize these findings.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 11/2010; 39(6):644-9.
[Show abstract][Hide abstract] ABSTRACT: This study describes the clinical and neuroimaging features of five patients with 1, 2-Dichloroethane (DCE) toxic encephalopathy. From January 1st 1998 to June 30th 2009, five patients who were subsequently diagnosed with DCE toxic encephalopathy were admitted to our hospital. All were female workers who had been in contact with DCE and subsequently had had seizures or symptoms of intracranial hypertension, including headache, nausea, and vomiting. The cranial MRI showed extensive brain edema in either the subcortical white matter, bilateral globus pallidus, and cerebellar nucleus dendatus, or the cortices. Of the five patients in the study, three had vasogenic edema, one had cytotoxic edema, and one had both types of edema. Following treatment with steroids and mannitol for 3 to 10 weeks, all patients made either a partial or complete recovery. The imaging findings were resolved on a follow-up MRI. It is clear that occupational exposure to DCE can cause severe toxic encephalopathy. Moreover, extensive brain edema, secondary to blood-brain barrier damage or neuronal injury, is the major neuroimaging feature and the cause of clinical manifestations. Early diagnosis and prompt treatment leads to a good outcome.
Journal of the neurological sciences 02/2010; 292(1-2):111-3. DOI:10.1016/j.jns.2010.01.022 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mouse stroke models provide experiment basis for study of the mechanisms of cell death and neural repair, and the neuroprotective effect of new drugs. There are at least three models of middle cerebral artery occlusion (MCAO) routinely used in experimental study. These models vary widely in their application in study of cell death or neural repair, and simulation of human diseases. This review article is focused on the characteristics of three mouse MCAO models and the strains-related differences in susceptibility to cerebral ischemia.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 09/2009; 38(5):541-6.
[Show abstract][Hide abstract] ABSTRACT: Cardiac right-to-left shunt (RLS), mainly due to patent foramen ovale (PFO), is a risk factor for paradoxical embolism and stroke. Results of studies about brain lesions in diffusion-weighted imaging (DWI) in PFO patients were controversial. DWI only detects acute ischemic lesions. We assessed the hypothesis that, in T2-weighted magnetic resonance imaging (T2WI) of stroke patients, RLS is associated with a typical distribution of small white matter lesions.
In this retrospective case-control study, T2WI images of 162 stroke patients were evaluated. From stroke patients admitted between 1999 and 2003, 81 stroke patients with RLS were identified with contrast-enhanced transcranial Doppler (bubble test). Controls were 81 age-matched stroke patients without RLS (negative bubble test). In T2WI images, small lesions (<2 cm) were categorized depending on their location in subcortical white matter, peritrigonal white matter, deep and paraventricular white matter, and basal ganglia. Additionally, larger territorial infarcts were rated.
In T2WI frontal or predominantly frontal-located subcortical small white matter, lesions are significantly associated with RLS (p < 0.0001, chi-square test). Forty-three patients with RLS (53%) and only 19 control patients (23%) showed this frontal dominance. Odds ratio is 3.7 (95% confidence interval = 1.9-7.1) for having a RLS when T2WI shows this lesion pattern in a stroke patient. No patient of the RLS group and 6% of the control group had parietal dominance. Distribution of small lesions in other locations like basal ganglia or deep white matter showed no significant difference for the groups.
A distribution of mainly frontal subcortical small white matter lesions in T2WI is significantly associated with RLS in stroke patients.
[Show abstract][Hide abstract] ABSTRACT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebrovascular disease caused by a mutation of the NOTCH3 gene. The clinical information of two CADASIL families was studied and mutation analysis of the NOTCH3 gene was performed by DNA direct sequencing. Published studies of Mainland Chinese CADASIL patients were reviewed and reanalyzed. The patients in the two families showed migraine with aura, stroke and cognitive decline. Cranial MRI revealed subcortical white matter infarcts and leukoencephalopathy. Two previously reported mutations of the NOTCH3 gene, c.397C>T and c.268C>T, were identified and cosegregated with the disease. The main clinical features, cranial MRI and pathological changes in Mainland Chinese CADASIL patients were similar to those in other regions. The frequency of migraine may be lower than that in Europe, but similar to that in Asia. Eight different NOTCH3 gene mutations were reported among Mainland Chinese CADASIL patients; of these, the c.322C>T mutation has not been reported in other regions. This study supports that the clinical features of Mainland Chinese CADASIL patients are similar to those seen in other regions and that exon 3 and exon 4 of the NOTCH3 gene are the mutation hotspots in Mainland Chinese CADASIL patients.
Journal of the neurological sciences 04/2009; 279(1-2):88-92. DOI:10.1016/j.jns.2008.12.011 · 2.47 Impact Factor